This project concerns clinical, preclinical, and biophysical studies of anti-cancer drugs. Clinically useful assays for citrovorum factor and 8-azaguanine in body fluids have been developed. The assay for 8-azaguanine has been used to study the pharmacokinetics of intraventricular administration in monkeys. Both assays are being applied to studies in man. Preclinical studies of systemic and cerebrospinal fluid pharmacokinetics in monkeys and dogs have been initiated on a variety of antineoplastic drugs. These studies are also being used to explore potentially useful interactions of chemotherapeutic agents with other drugs. An electric dichroism apparatus has been constructed for use in characterizing interactions of small molecules (carcinogens and anticarcinogens) with macromolecules of biological importance. Such measurements may be helpful in evaluating analogues of known and newly proposed drugs. The results may also permit the use of small molecules as probes of subcellular structure. We are also investigating new treatments for patients with CNS leukemia, based on an innovative primate model which allows direct access to the ventricular cerebrospinal fluid, and thus facilitates investigation of CSF pharmacokinetics. BIBLIOGRAPHIC REFERENCE: Wood, J.H., Poplack, D.G., Bleyer, W.A., Ommaya, A.K.: Primate model for the chronic study of intraventricularly or intrathecally-administered drugs, and intracranial pressure. Science 195: 499-501, 1977.